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Notes: Abstract: We have investigated the effect of unsaturated free fatty acids (FFAs) on the brain GABA/benzodiazepine receptor chloride channel complex from mammalian, avian, amphibian, and fish species in vitro. Unsaturated FFAs with a carbon chain length between 16 and 22 carbon atoms enhanced [3H]diazepam binding in rat brain membrane preparations, whereas the saturated analogues had no effect. The enhancement of [3H]diazepam binding by oleic acid was independent of the incubation temperature (0-30°C) of the binding assay and not additive to the enhancement by high concentrations of C1. In rat brain preparations, the stimulation of [3H]diazepam binding by oleic acid (10−4M) was independent of the ontogenetic development. Phylogenetically, large differences were found in the effect of unsaturated FFAs on [3H]diazepam and [3H]muscimol binding: In mammals and amphibians, unsaturated FFAs enhanced both [3H]-muscimol and [3H]diazepam binding to 150-250% of control binding. In 17 fish species studied, oleic acid (10−4M) stimulation of [3H]diazepam binding was weak (11 species), absent (four species), or reversed to inhibition (two species), whereas stimulation of [3H]muscimol binding was of the same magnitude as in mammals and amphibians. In 10 bird species studied, only weak enhancement of [3H]muscimol binding (110–130% of control) by oleic acid (10−4M) was found, whereas [3H]diazepam binding enhancement was similar to values in mammal species. Radiation inactivation of the receptor complex in situ from frozen rat cortex showed that the functional target size for oleic acid to stimulate [3H]flunitrazepam binding has a molecular mass of ∼200,000 daltons. Our data show that unsaturated FFAs have distinct effects on membranebound GABA/benzodiazepine receptors in vitro.

Notes: Summary A retrospective study was performed to evaluate the ability to predict sperm-surface antisperm antibodies (ASA) in patients with primary infertility on the basis of semen analysis. In particular, the ability to predict ASA status on the basis of impaired sperm motility was assessed. The clinical and seminal characteristics of 70 consecutive ASA-positive infertility patients detected by routine screening were reviewed. Similar analysis was performed on 128 consecutive patients with infertility who were found on routine screening to be ASA-negative. The association between the presence of ASA and sperm motility, concentration, and clumping was examined using multivariate analysis. Two variables were found to have a significant joint association with the presence of ASAs. Patients with sperm concentrations of 〉20 million/ml were significantly more likely to be ASA-positive (P=0.002). Second, after adjustment for sperm concentration, patients with lower motilities were significantly more likely to be ASA-positive (P=0.016). Although impaired motility was seen significantly more often in ASA-positive patients, this seminal defect alone should not be used for predictive screening, since 39% of ASA-positive patients had sperm motilities of 〉60%. Furthermore, when a normal sperm concentration (〉20 million/ml) was combined with impaired sperm motility (〈60%) as an indication for ASA testing in this population, the result was a sensitivity of only 43%, a specificity of 77%, and positive and negative predictive values of 50% and 77%, respectively. Despite the association between normal sperm concentrations and impaired motility, it appears that the results of semen analysis cannot be used as a sole indication for ASA testing.

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Notes: Abstract 1. The bark of the root and stem of various Magnolia species has been used in Traditional Chinese Medicine to treat a variety of disorders including anxiety and nervous disturbances. The biphenolic compounds honokiol (H) and magnolol (M), the main components of the Chinese medicinal plant Magnolia officinalis, interact with GABAA receptors in rat brain in vitro. We compared the effects of H and M on [3H]muscimol (MUS) and [3H]flunitrazepam (FNM) binding using EDTA/water dialyzed rat brain membranes in a buffer containing 150 mM NaCl plus 5 mM Tris-HCl, pH 7.5 as well as [35S]t-butylbicyclophosphorothionate (TBPS) in 200 mM KBr plus 5 mM Tris-HCl, pH 7.5. H and M had similar enhancing effects on [3H]MUS as well as on [3H]FNM binding to rat brain membrane preparations, but H was 2.5 to 5.2 times more potent than M. 2. [ 3 H]FNM binding. GABA alone almost doubled [3H]FNM binding with EC50 = 450 nM and 200 nM using forebrain and cerebellar membranes, respectively. In the presence of 5 μM H or M the EC50 values for GABA were decreased to 79 and 89 nM, respectively, using forebrain, and 39 and 78 nM, using cerebellar membranes. H and M potently enhanced the potentiating effect of 200 nM GABA on [3H]FNM binding with EC50 values of 0.61 μM and 1.6 μM using forebrain membranes, with maximal enhancements of 33 and 47%, respectively. Using cerebellar membranes, the corresponding values were 0.25 and 1.1 μM, and 22 and 34%. 3. [ 3 H]MUS binding. H and M increased [3H]MUS binding to whole forebrain membranes about 3-fold with EC50 values of 6.0 and 15 μM. Using cerebellar membranes, H and M increased [3H]MUS binding ~68% with EC50 values of 2.3 and 12 μM, respectively. Scatchard analysis revealed that the enhancements of [3H]MUS binding were due primarily to increases in the number of binding sites (Bmax values) with no effect on the high affinity binding constants (Kd values). The enhancing effect of H and M were not additive. 4. [ 35 S]TBPS binding. H and M displaced [35S]TBPS binding from sites on whole rat forebrain membranes with IC50 values of 7.8 and 6.0 μM, respectively. Using cerebellar membranes, the corresponding IC50 values were 5.3 and 4.8 μM. These inhibitory effects were reversed by the potent GABAA receptor blocker R5135 (10 nM), suggesting that H and M allosterically increase the affinity of GABAA receptors for GABA and MUS by binding to sites in GABAA receptor complexes. 5. Two monophenols, the anesthetic propofol (2,6-diisopropylphenol, P) and the anti-inflammatory diflunisal (2′,4′-difluoro-4-hydroxy-3-biphenyl carboxylic acid, D) also enhanced [3H]MUS binding, decreased the EC50 values for GABA in enhancing [3H]FNM binding and potentiated the enhancing effect of 200 nM GABA on [3H]FNM binding, although enhancements of [3H]MUS binding for these monophenols were smaller than those for H and M, using forebrain and cerebellar membranes. The enhancing effect of P and D on [3H]MUS binding were almost completely additive. 2,2′-biphenol was inactive on [3H]MUS and [3H]FNM binding. These, and other preliminary experiments, suggest that appropriate ortho (C2) and para (C4) substitution increases the GABA-potentiating activity of phenols. 6. The potentiation of GABAergic neurotransmission by H and M is probably involved in their previously reported anxiolytic and central depressant effects.

Notes: Die Umsetzung der Achtringverbindung S4N4O2 mit mehrfach substituierten Silylaminen und Tris(trimethylstannyl)amin führt zu den Sechs- bzw. Achtring-Heterocyclen 1-3. Die Sechsringe 1 und 2 sind die ersten Beispiele, in denen der Schwefel die formalen Oxidationsstufen 2, 4 und 6 erreicht. 1 und 2 lassen sich auch durch Umsetzung von N-Sulfinylfluorsulfonamid mit silyl- oder stannylsubstituiertem Schwefeldiimid darstellen. 2 und 3 sind ebenfalls zugänglich durch die Umsetzung von S4N4O2 mit Trimethylzinnazid. Die Struktur von 2 wurde durch eine Röntgen-analyse aufgeklärt. 2 kristallisiert in der Raumgruppe P21. Fünf der sechs Ringatome bilden eine Ebene, während das Stickstoffatom, welches am Zinnatom gebunden ist. um 78 pm außerhalb der Ringebene liegt. Die S — N-Bindungslängen werden im Zusammenhang mit bisher bekannten Strukturen diskutiert.

Notes: Die Umsetzung von S4N4O2 mit Nucleophilen (Alkoholate, Alkohole, Azide und Isocyanate) in alkoholischem Medium führt zu den Salzen 1a-h. Für 1h wurde eine Röntgenstrukturanalyse durchgeführt. 1h kristallisiert in der Raumgruppe P21/n und enthält eine transannulare S—S Bindung mit 248.2 (2) pm. Die Struktur von 1h wird im Zusammenhang mit der Zunahme der Elektronendichte betrachtet und mit den Ergebnissen der Röntgenstrukturanalyse von CH3Si(NSN)3SiCH3 (2) verglichen. 2 kristallisiert kubisch (Raumgruppe P4132). Das bicyclische Molekül (S—N 150.4 (2), Si—N 173.7 (2)pm) hat praktisch D3h Symmetrie und zeigt keine S—S-Bindungen im Ring.